The long-term objective of this research proposal is to define the role of retinal lipids and retinal lipid metabolism in health and disease. This will be carried out using a variety of in vitro and in vivo models. The mechanism of selective enrichment for 22:6n-3 in the retina will be explored in retinal homogenates using labeled glycerol and pulse-chase methods. The question of de novo lipid synthesis versus post-synthesis lipid remodeling will be investigated. In addition, studies not completed during the current funding period will be continued using rats raised in high- and low-intensity light environments. These rats will be challenged with the pro-oxidant ferrous sulfate to determine their relative capabilities to defend their retinas with endogenous antioxidants, which appear to be upregulated by high-intensity light environments. Studies will also be continued that explore the role of 22:6 in inherited retinal disease using the prcd poodle as a model. Particular emphasis will be placed on the possibility that trafficking of 22:6 is abnormal in these dogs based upon the finding that their blood levels are low. Lastly, the pathways for the formation of some 14 carbon fatty acids will be investigated, as well as their incorporation into retinal proteins.